Biomolecular filters for improved separation of output signals in enzyme logic systems applied to biomedical analysis.

Biomolecular logic systems processing biochemical input signals and producing "digital" outputs in the form of YES/NO were developed for analysis of physiological conditions characteristic of liver injury, soft tissue injury, and abdominal trauma. Injury biomarkers were used as input signals for activating the logic systems. Their normal physiological concentrations were defined as logic-0 level, while their pathologically elevated concentrations were defined as logic-1 values. Since the input concentrations applied as logic 0 and 1 values were not sufficiently different, the output signals being at low and high values (0, 1 outputs) were separated with a short gap making their discrimination difficult. Coupled enzymatic reactions functioning as a biomolecular signal processing system with a built-in filter property were developed. The filter process involves a partial back-conversion of the optical-output-signal-yielding product, but only at its low concentrations, thus allowing the proper discrimination between 0 and 1 output values.

[1]  A. P. Silva,et al.  A supramolecular chemistry basis for molecular logic and computation , 2007 .

[2]  E. Katz,et al.  Bio-logic analysis of injury biomarker patterns in human serum samples. , 2011, Talanta.

[3]  Jian Zhou,et al.  Enzyme logic gates for the digital analysis of physiological level upon injury. , 2009, Biosensors & bioelectronics.

[4]  Gonen Ashkenasy,et al.  Boolean logic functions of a synthetic peptide network. , 2004, Journal of the American Chemical Society.

[5]  Vladimir Privman,et al.  Biochemical Filter with Sigmoidal Response: Increasing the Complexity of Biomolecular Logic , 2010, The journal of physical chemistry. B.

[6]  B. Reiser,et al.  Estimation of the area under the ROC curve , 2002, Statistics in medicine.

[7]  Naftali Tishby,et al.  Stochastic computing with biomolecular automata , 2004, Proc. Natl. Acad. Sci. USA.

[8]  J. Henry.  Clinical diagnosis and management by laboratory methods , 1979 .

[9]  Christopher A. Voigt,et al.  Robust multicellular computing using genetically encoded NOR gates and chemical ‘wires’ , 2011, Nature.

[10]  Vladimir Privman,et al.  Enzyme-based logic systems for information processing. , 2009, Chemical Society reviews.

[11]  Jian Zhou,et al.  Stimuli-responsive hydrogel membranes coupled with biocatalytic processes. , 2009, ACS applied materials & interfaces.

[12]  Stephen D. Walter.  False Positive Rate , 2005 .

[13]  Vladimir Privman,et al.  Towards Biochemical Filter with Sigmoidal Response to pH Changes: Buffered Biocatalytic Signal Transduction , 2010, Physical chemistry chemical physics : PCCP.

[14]  Uwe Pischel,et al.  Chemical approaches to molecular logic elements for addition and subtraction. , 2007, Angewandte Chemie.

[15]  Joseph Wang,et al.  Enzymatic AND logic gates operated under conditions characteristic of biomedical applications. , 2010, The journal of physical chemistry. B.

[16]  Uwe Pischel,et al.  Smart molecules at work--mimicking advanced logic operations. , 2010, Chemical Society reviews.

[17]  Jian Zhou,et al.  Multi-enzyme logic network architectures for assessing injuries: digital processing of biomarkers. , 2010, Molecular bioSystems.

[18]  Ernest Beutler,et al.  Glucose-6-phosphate dehydrogenase deficiency: a historical perspective. , 2008, Blood.

[19]  J. Wallach.  Interpretation of Diagnostic Tests , 1996 .

[20]  Jian Zhou,et al.  Boolean-format biocatalytic processing of enzyme biomarkers for the diagnosis of soft tissue injury , 2010 .

[21]  Yaakov Benenson,et al.  Biocomputers: from test tubes to live cells. , 2009, Molecular bioSystems.

[22]  John Moult,et al.  Towards computing with proteins , 2006, Proteins.

[23]  E.E. May,et al.  Towards De Novo Design of Deoxyribozyme Biosensors for GMO Detection , 2008, IEEE Sensors Journal.

[24]  Evgeny Katz,et al.  Digital biosensors with built-in logic for biomedical applications—biosensors based on a biocomputing concept , 2010, Analytical and bioanalytical chemistry.

[25]  M. Rosemeyer.  The biochemistry of glucose‐6‐phosphate dehydrogenase, 6‐phosphogluconate dehydrogenase and glutathione reductase , 1987, Cell biochemistry and function.

[26]  Jan Halámek,et al.  Responsive interface switchable by logically processed physiological signals: toward "smart" actuators for signal amplification and drug delivery. , 2011, ACS applied materials & interfaces.

[27]  Ehud Shapiro,et al.  Towards molecular computers that operate in a biological environment , 2008 .

[28]  Jian Zhou,et al.  Multiplexing of injury codes for the parallel operation of enzyme logic gates. , 2010, The Analyst.

[29]  Ehud Shapiro,et al.  Biotechnology: logic goes in vitro. , 2007, Nature nanotechnology.

[30]  Michael J Sailor,et al.  Nanoparticle self-assembly gated by logical proteolytic triggers. , 2007, Journal of the American Chemical Society.

[31]  Z. Ezziane.  DNA computing: applications and challenges , 2006 .

[32]  P. London.  Injury , 1969, Definitions.

[33]  Evgeny Katz,et al.  Bacteria-based AND logic gate: a decision-making and self-powered biosensor. , 2011, Chemical communications.

[34]  R. Pearl.  Biometrics , 1914, The American Naturalist.

[35]  A. Credi.  Molecules that make decisions. , 2007, Angewandte Chemie.

[36]  K. Szaciłowski.  Digital information processing in molecular systems. , 2008, Chemical reviews.

[37]  M. Zweig,et al.  Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. , 1993, Clinical chemistry.

[38]  Vladimir Privman,et al.  Control of Noise in Chemical and Biochemical Information Processing , 2010, ArXiv.

[39]  M. Chiu,et al.  Hepatic enzymes have a role in the diagnosis of hepatic injury after blunt abdominal trauma. , 2009, Injury.

[40]  R. Weiss,et al.  A universal RNAi-based logic evaluator that operates in mammalian cells , 2007, Nature Biotechnology.